By Sebastian Kmiecik, Researcher at the Laboratory of Theory of Biopolymers, University of Warsaw

Researchers from the Laboratory of Theory of Biopolymers at the University of Warsaw have developed CABS-dock, a new computational method (available as a web server) which allows predicting the structure of protein-peptide complexes and uses no knowledge about the peptide binding site nor the peptide conformation. The method utilizes highly efficient simulation approach for molecular docking of peptides to proteins.

Protein-peptide interactions play a key role in cell functions. Their structural characterization, though challenging, is important for the discovery of new drugs. The CABS-dock web server provides an interface for modeling protein-peptide interactions using a highly efficient protocol for the flexible docking of peptides to proteins. While other docking algorithms (like Rosetta FlexPepDock or HADDOCK) require pre-defined localization of the binding site, CABS-dock doesn’t require such knowledge. Given a protein receptor structure and a peptide sequence (and starting from random conformations and positions of the peptide), CABS-dock performs simulation search for the binding site allowing for full flexibility of the peptide and small fluctuations of the receptor backbone. This protocol was extensively tested over the largest dataset of non-redundant protein-peptide interactions available to date (including bound and unbound docking cases). For over 80% of bound and unbound dataset cases, high or medium accuracy models were obtained (sufficient for practical applications). The performance summary is presented in the Figure below.

Figure caption. CABS-dock performance summary for 103 bound and 68 unbound benchmark cases. The percentages of high-, medium- or low-accuracy models (high accuracy: rmsd<3 Å; medium accuracy: 3 Å ≤ rmsd ≤ 5.5 Å; low accuracy: rmsd > 5.5 Å) are reported for the best quality models found in the sets of 10 000 models (all) and in the sets of 10 final models (top 10). Figure is taken from the CABS-dock paper [Nucleic Acids Res, 2015, doi: 10.1093/nar/gkv456].Entire benchmark results are available in the online CABS-dock materials at http://biocomp.chem.uw.edu.pl/CABSdock/benchmark

Additionally, as optional features, CABS-dock enables to exclude user-selected binding modes from docking search or to increase the level of flexibility for chosen receptor fragments. CABS-dock is freely available as a web server at http://biocomp.chem.uw.edu.pl/CABSdock

Video description: An example simulation of protein-peptide molecular docking using CABS-dock web server. In the movie, the assembly of major histocompatibility complex (MHC)-peptide structure is simulated. Experimental peptide structure is shown in green, while the simulated peptide in red. The movie shows 1 of 10 trajectories generated in a standard CABS-dock simulation run. The predicted peptide structure, shown at the simulation end, differs from the experimental structure by 1.8 Ångstroms.

Though I like posting them, and some of the readers like sifting through, the literature reviews always struck me as too static, I wanted to have a more nimble system that can allow readers to comment on a specific paper, to ‘like’ specific papers, and to be able to sort the list this way or another. Following the recent post on Annotator, it came to mind that Disqus might indeed be the answer for a few of these problems. So here is a pilot for this approach, let’s see how it goes. All the titles are posted as comments at the bottom, you can comment/ask questions on specific ones, show appreciation by ‘liking’ them, sort by popularity, moreover – you can add all the ones I missed!

The latest crop of interesting literature in our field. There are a bunch of papers about protein dynamics (and its conservation) and another bunch on protein design. And if you search carefully there is also one paper by us on peptide docking with a new Rosetta protocol.

Another compilation of forty some titles from the recent literature all about your favorite computational structural biology science. Two of the papers are by Rosetta Design Group’s members – see if you can find waldo. Enjoy.